Key result
Five-locus genetic risk score is linked to ~19% higher CHD odds per unit in T2D.
Why the study?
No study had examined whether coronary heart disease susceptibility loci identified in the general population also contribute to coronary heart disease in patients with type 2 diabetes.
Do coronary heart disease-susceptibility loci identified in the general population also predict coronary heart disease in patients with type 2 diabetes?
Case-Control (n=2,506)
Yes
Do coronary heart disease-susceptibility loci identified in the general population also predict coronary heart disease in patients with type 2 diabetes?
Odds Ratio: 1.19 (95% CI 1.13–1.26)
p-value: p=<0.0001
Genetic risk variants associated with coronary heart disease in the general population also predict CHD in type 2 diabetes and modestly improve risk prediction beyond traditional clinical risk factors.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“The effect is not dramatic, but it is much better than what we expected”
“If we find additional variants, we may be able to develop a tool that identifies diabetic patients who are at increased risk of developing CHD and focus on preventing the disease in these people”
Genetic scores may refine CHD prediction in diabetes; extends general-population loci but remains hypothesis-generating without prospective validation.
Objective To evaluate whether coronary heart disease (CHD)-susceptibility loci identified by genome-wide association studies of the general population also contribute to CHD in type 2 diabetes. Background No study has examined the effects of these genetic variants on CHD in diabetic patients. Methods We genotyped 15 genetic markers of 12 loci in three studies of diabetic patients: the prospective Nurses’ Health Study (309 CHD cases and 544 controls) and Health Professional Follow-up Study (345 CHD cases and 451 controls), and the cross-sectional Joslin Heart Study (422 CHD cases and 435 controls). Results Five SNPs, rs4977574 (CDKN2A/2B), rs12526453 (PHACTR1), rs646776 (CELSR2-PSRC1-SORT1), rs2259816 (HNF1A), and rs11206510 (PCSK9) showed directionally consistent associations with CHD in the three studies, with combined odds ratios (ORs) ranging from 1.17 to 1.25 (p=0.03 to 0.0002). None of the other SNPs reached significance in individual or combined analyses. A genetic risk score (GRS) was created by combining the risk alleles of the five significantly associated loci. The OR of CHD per GRS unit was 1.19 (95% confidence interval [CI] 1.13– 1.26; p<0.0001). Individuals with GRS ≥8 (19% of diabetic subjects) had almost a two-fold increase in CHD risk (OR=1.94, 95% CI 1.60–2.35) as compared to individuals with GRS ≤5 (30% of diabetic subjects). Prediction of CHD was significantly improved (p<0.001) when the GRS was added to a model including clinical predictors in the combined samples. Conclusions Our results illustrate the consistency and differences in the determinants of genetic susceptibility to CHD in diabetic patients and the general populations.
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Qi et al. (2011) conducted a case-control in Type 2 Diabetes and Coronary Heart Disease (n=2,506). Genetic risk score (5 CHD-susceptibility SNPs) vs. Lower genetic risk score was evaluated on Coronary heart disease per genetic risk score unit (OR 1.19, 95% CI 1.13-1.26, p=<0.0001). A genetic risk score combining five susceptibility loci was significantly associated with coronary heart disease in patients with type 2 diabetes, conferring an odds ratio of 1.19 per score unit.
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